A large number of near patient analyses are performed every day in hospitals, in primary health care and at home. In a frequent method, a measured sample volume of the patient's body fluid (for instance blood, plasma, urine, sweat, tears, lymph, amniotic fluid, cerebrospinal fluid and faeces) is collected in a capillary tube and transferred to a container, after which it is exposed to various specific reagents with which the body fluid reacts. The final quantitative or qualitative chemical analysis is performed by means of an optical detector in a transparent cuvette or on a measuring surface. The devices (for instance QuikRead manufactured by Axis Shield A/S, Norway) which are based on a manual method imply that the sample volume and reagent solutions may be spilt on people or work surfaces, resulting in health and environmental hazards. There is also a risk of incorrect analytical results due to laboratory mishandling. The devices (for instance Afinion manufactured by Axis Shield A/S, Norway) which are based on automated methods reduce the above-mentioned health and environmental hazards and also the risk of incorrect analytical results, but this is done by a costly and complex technical solution.
The specific reagents that are used are of the type biochemically (that is biologically and chemically) reactive substances, which may consist of monoclonal antibody, polyclonal antibody, enzyme, inorganic oxidising agents, inorganic reducing agents, metal ions, metal ion complexes, proteins, hormones, complementary factors, bacteria, cells, virus, fungi, yeast, spores, phages, cell organelles, peptides, DNA, RNA, coagulation inhibiting substances, cell lysing agents, antibiotics, tenside and active detergents.
After the body fluid having reacted with one or more specific reagents, this biological or chemical event is transformed into a physical change (optical, electric, radioactive or magnetic), which can be perceived by a detector. Optical detectors are popular especially in established immunoassay technologies that are used for near patient analyses. Optical detectors measure, inter alia, changes of the absorption of light, light scattering, fluorescence, polarisation, and require transparent cuvettes with transparent liquid sample contents. This results in the drawback that the liquid sample frequently has to be biochemically processed in several steps before it reaches the transparent cuvette or measuring surface. Electric detectors must be in direct contact with the liquid sample and therefore are sensitive to disturbing substances such as ascorbic acid in the body fluid. Radioactive detectors are rare in near patient analyses since they are a danger to people and environment. Magnetic detectors measure, inter alia, magnetic permeability and have the advantage that they allow quick and easy detection of the contents in non-transparent cuvettes which are allowed to contain non-transparent fluid, suspension, and capillary tubes. Such a magnetic detector is disclosed in SE9502902-1, U.S. Pat. No. 6,110,660 and Larsson K. et al. Analusis 27, p 78 1999.
The present invention solves the above described problems in a new and effective way by offering the user a manually operable disposable device to provide leakage-free biochemical processing and analysis of a measured sample volume of a liquid sample with an eliminated risk of contamination of people and environment and a minimised risk of incorrect measured values without using instruments with automatic preparation of samples.
The above-mentioned commercially available devices and documents SE9502902-1 (Dario Kriz, 1995) U.S. Pat. No. 6,110,660 (Dario Kriz, 1995) and Larsson K. et al. (Analusis 27, p 78, 1999) describe prior art devices and methods that are used for chemical processing and analysis of a measured sample volume of a liquid sample. However, said devices and methods do not contain a thin pierceable membrane through which an arm-fixed capillary tube passes and fits tightly around the arm after the insertion of the capillary tube. The present invention enables a manually operable disposable device to provide leakage-free biochemical processing and analysis of a measured sample volume of a liquid sample with an eliminated risk of contamination of people and environment and a minimised risk of incorrect measured values due to reagent losses related to leakage of liquid without using instruments with automatic preparation of samples and without necessitating a negative pressure or an injection mechanism in the inventive device.
Other prior art techniques comprise a liquid sample collecting device according to WO 79/01131 (Robert Turner and Reginald Holman, 1978). This device comprises a pierceable flexible membrane which is penetrated by a capillary tube. The membrane fits tightly around the capillary tube, of which each end is on an associated side of the membrane. To allow the sample volume in the capillary tube to be drawn into the device there is a negative pressure in the device. The present invention does not require a negative pressure since both ends of the capillary tube pass the membrane and the sample volume is shaken out of the capillary tube. Furthermore the device according to WO 79/01131 doe not contain any substances for biochemical processing and analysis.
Other prior art techniques comprise a sample collecting device according to U.S. Pat. No. 5,833,630 (Bernd Kloth, 1997). This device comprises a capillary tube and substances for biochemical processing and analysis. The device does not comprise a pierceable membrane which is penetrated by the capillary tube. The capillary tube is positioned in a duct in a stopper which is placed on the device. The capillary tube is pressed into (but not through) the stopper by means of a cap, the generated positive pressure forcing the sample volume out of the capillary tube and down into the device. Since the device does not have a pierceable membrane and requires manual exchange of the stopper (from a stopper without capillary tube to one with capillary tube), there is a risk of some spilling of the reagent solution of the device, which results in incorrect measured results. Moreover the emptying of the capillary tube will not be as quick and effective as in the present invention since the forced liquid movement through the capillary tube in the present invention cleans the capillary tube without leaving any residues of adsorbed sample solution.
Other prior art techniques comprise a device for handling organic body fluids according to SE451942 (Bengt-Inge Brodén, 1986). This device comprises a capillary tube but no substances for biochemical processing and analysis. The device does not comprise a pierceable membrane which is penetrated by the capillary tube. The capillary tube is positioned in a duct in a stopper which is placed on the device. Air is forced through the capillary tube by means of a sprayer, the generated positive pressure forcing the sample volume out of the capillary tube and down into the device. The device does not contain any substances for chemical processing and analysis and is designed to reduce the risk of contamination caused by spilling of body fluid samples. Furthermore the emptying of the capillary tube will not be as quick and effective as with the present invention since the forced liquid movement through the capillary tube in the present invention cleans the capillary tube without leaving any residues of adsorbed sample solution.
Other prior art techniques comprise a combination reagent and test device for analysing liquids according to U.S. Pat. No. 5,888,826 (Roy Ostgaard et el., 1997). This device comprises a pierceable membrane and substances for biochemical processing and analysis. The device does not comprise a capillary tube and is not designed for manual handling (mixing of sample solution and reagent) but requires advanced automatic instruments for function.
Other prior art techniques comprise a disposable device for analysing liquids according to U.S. Pat. No. 6,319,209 (Dario Kriz, 1999). This device comprises a capillary tube and substances for biochemical processing and analysis. Since the device does not have a pierceable membrane and requires manual turning of a stopper (from one without to one with capillary tube) there is a risk of some spilling of the reagent solution of the device, which results in incorrect measured results. Moreover the emptying of the capillary tube will not be as quick and effective as in the present invention since the forced liquid movement through the capillary tube in the present invention cleans the capillary tube without leaving any residues of adsorbed sample solution.